This invention relates generally to treatment of neonatal hyperbilirubinemia (jaundice). More particularly, it relates to phototherapy methods and devices containing light-emitting diodes.
Approximately 60% of the four million infants born in the United States each year become clinically jaundiced. Jaundice, or hyperbilirubinemia, results from increased production and transiently impaired elimination of the pigment bilirubin. While most affected neonates recover rapidly, some infants show persistent high levels of unconjugated bilirubin. Such high levels can lead to kernicterus, a condition involving deposition of bilirubin in the brain, which leads to deficits in cognition, neuromuscular tone and control, and hearing, and even death. The most common therapy for neonatal hyperbilirubinemia is phototherapy. It is estimated that as many as 400,000 neonates in the United States receive phototherapy every year.
Phototherapy facilitates the transformation of unconjugated bilirubin to compounds that are more easily excreted. Bilirubin undergoes in parallel three reactions: photooxidation, configurational isomerization, and structural isomerization. Structural isomerization is the predominant mechanism leading to bilirubin elimination from the bloodstream. Structural isomerization transforms bilirubin instantaneously and continuously into the more polar non-toxic pigment lumirubin, which is presumably the major bilirubin product excreted in newborns undergoing phototherapy. The wavelength range generally effective for facilitating bilirubin photoisomerization is approximately 400-550 nm (violet to green), with light of a wavelength between 450 and 460 nm (blue) yielding maximal photoisomerization. For general information on hyperbilirubinemia and phototherapy, see for example the articles by the Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia (American Academy of Pediatrics) in Pediatrics 94:558-565 (1994), Ennever in Clin. Perinatol. 17:467-481 (1990), and Maisels in Neonatology: Pathophysiology and Management of the Newborn, 4th Edition, J. B. Lippincott Co., Philadelphia, p. 630-735, as well as the books by Volpe, Neurology of the Newborn, W. B. Saunders Co., Philadelphia, 1995, and Brown and McDonagh, Phototherapy for Neonatal Hyperbilirubinemia: Efficacy, Mechanism, and Toxicity, Year-Book Medical Publishers, 1980.
The efficacy of phototherapy depends on four main factors: irradiance (light intensity), spectral range (wavelength or color), exposed skin surface area, and duration of exposure. Irradiance is a measurement of the light energy incident on the skin, in units of xcexcW/cm2/nm (power per surface area per wavelength). For a given light source power, the irradiance can be increased by decreasing the distance between the light source and the newborn. Lumirubin formation is not only wavelength-dependent, but is also stimulated by higher light intensities, as discussed in the article by G. Agati et al. in J. Photochem. Photobiol., B: Biol. 17:173-180 (1993). Proper evaluation of phototherapy devices and techniques requires assessment of each of these four factors, as well as consideration of potential side effects.
Phototherapy for treating hyperbilirubinemia is commonly delivered using fluorescent lamps suspended above the neonate. However, these conventional phototherapy devices have substantial drawbacks. While fluorescent lamps output high-intensity light, they also generate significant heat (infrared radiation), which prevents their placement close to the infant, thereby decreasing the irradiance. Fluorescent light is of a broad spectral range, and cannot be produced in only the narrow wavelength range desired. Conventional phototherapy devices typically illuminate the newborn only from above, and do not therefore make optimal use of the available skin area. U.S. Pat. No. 3,877,437 to Maitan et al. describes an apparatus for simultaneous bilateral phototherapy of neonates, from both above and below, thus effectively doubling the exposed surface area of the infant. The apparatus uses fluorescent lamps and thus subjects the neonate to side effects discussed below.
The use of fluorescent lamps for phototherapy leads to adverse side effects in many newborns. Such side effects include increased insensible water loss, hypothermia, loose and frequent bowel movements, tanning, and potential nasal obstruction by the eye pads required for preventing retinal damage. Furthermore, there are concerns that phototherapy using fluorescent lamps has potentially harmful effects on biological rhythms, and may increase the incidence of skin cancer in neonates subject to repeated treatment. For information on potential side effects of conventional phototherapy treatment see the articles by Wu and Moosa in Pediatrics 61:193-198 (1978), Oh and Karecki in Am. J. Dis. Child 124:230-232 (1972), Bell et al. in J. Pediatr. 94:810-813 (1979), Woody and Brodkey in J. Pediatr. 82:1042-1043 (1973), Messner in Ped. Res. (Abstr.) 12:530 (1978), Kemper et al. in Pediatrics 84:773-778 (1989), and Garden et al. in Arch. Dermatol. 121:1415-1420 (1985). In addition, overhead illumination with AC-powered blue light leads to discomfort and vertigo in nursery staff, as explained for example in the article by Wanamaker et al. in Lighting, Research, and Technology 7:19 (1975).
Further drawbacks are introduced by the practical design of fluorescent lamps used for phototherapy. The bulky overhead lamps prevent unimpeded access to the baby and interfere with maternal-infant bonding. There is abundant literature regarding possible long-term harm stemming from disturbed maternal-infant bonding. For example, see Monogr. Soc. Res Child Dev. 64(3):67-96 (1999) and discussion on pages 213-220; and J. Child Psychol. Psychiatry 40(6):929-939 (1999). In the past, newborns typically remained in the hospital for at least three days, and hyperbilirubinemia was treated aggressively during this time. Now, however, most newborns are discharged within 24 or 36 hours, and bilirubin concentrations reach much higher levels before the problem is noticed. Such infants must be readmitted to the hospital for conventional phototherapy treatment, because phototherapy devices are not suitable for home use. Changing conditions demand phototherapy devices that are less expensive and more flexible to use, and particularly those that can be used at home by parents.
Several manufacturers have recently introduced fiberoptic phototherapy systems. Such manufacturers include Ohmeda (Columbia, Md.) and Fiberoptic Medical Products, Inc. (Allentown, Pa.). Typically, light from an incandescent xcx9c150 W tungsten-halogen bulb is delivered to a fiberoptic pad containing interwoven optical fibers having multiple scattering centers. The ends of all of the fibers are bundled together to form a cable into which the light source is directed. When the cable becomes too large in diameter, it is no longer convenient or feasible to use; thus the total optical power delivered to the pad is limited by the cable size. While the fiberoptic pads can be placed adjacent to the neonate (e.g. directly around the infant), the pad sizes and light intensities available with such systems are limited. For a given light source, enlarging the pad requires distributing the light over a greater area, thus reducing the irradiance. To achieve high levels of irradiance, manufacturers must compromise the surface area by reducing the size of the pad, thereby exposing a relatively small surface area of the newborn to the light. Descriptions of fiberoptic phototherapy systems are provided in U.S. Pat. No. 4,234,907 to Daniel and U.S. Pat. No. 5,339,223 to Kremenchugsky et al. For a comparative analysis of two commonly used fiberoptic phototherapy devices, see the article by George and Lynch in Clinical Pediatrics, Mar. 1994: 178-180. The authors note the desirability of higher light intensities, and conclude that xe2x80x9cin the past, perhaps too much attention has been paid to color and not enough attention has been paid to intensity.xe2x80x9d Furthermore, Ennever et al. in J. Pediatr. 109:119-122 (1986) suggest that xe2x80x9cif a method for conveniently delivering phototherapy of much higher intensity were developed without attendant problems associated with high intensity, tungsten filament sources, it could provide substantial improvement in the efficacy of phototherapy.xe2x80x9d
For further information and analysis of prior art light sources, see the articles by Pratesi et al. in Photodermatology 6:244-257 (1989), Donzelli and Pratesi in SPIE Proceedings of Biomedical Optoelectronic Devices and Systems 2084:332-344 (1994), and Donzelli et al. in The Lancet 346:184-185 (1995).
Recently, devices have been developed that attempt to overcome the problems of low intensity and minimal surface area coverage of prior art phototherapy systems. A thin panel illuminator is disclosed in U.S. Pat. No. 5,005,108 to Pristash et al. Light is input to a transparent panel, conducted through the panel, and then emitted from one of its surfaces. The panel is flexible and may be shaped around a body part for optimum delivery of light to the required areas. However, this panel suffers from the same intensity problem as fiberoptic panels. The light is generated in a location that is a distance away from the location of its delivery to the skin, and the resulting power delivered is lower than desirable for phototherapy applications.
U.S. Pat. No. 5,698,866 to Doiron et al. discloses a uniform illuminator for local phototherapy using light-emitting diodes (LEDs) as a light source. LEDs provide significant advantages over fluorescent lamps or fiberoptic systems: narrow spectrum, high intensity at desired wavelengths, small size, relatively low cost, and ability to generate light in direct contact with the skin surface. The illuminator of Doiron includes a handpiece containing an LED array that is connected to a power source. The LEDs are fixed in a particular plane defined by the handpiece. While the device does provide a high irradiance, it covers only a very small region of the skin, and therefore cannot provide the surface area exposure required for treating hyperbilirubinemia using total body phototherapy.
A flexible pad containing diodes used for photo-thermal therapy is disclosed in U.S. Pat. No. 5,358,503 to Bertwell et al. Over a given skin region, the pad""s flexibility allows all of the diodes to be positioned with their longitudinal axes perpendicular to the skin. However, the device is not suitable for covering a large surface area of a neonate, which requires it to conform to the infant""s skin and therefore make sharp folds. The lens-type diodes used are also not suitable for supporting the neonate""s weight. Finally, the pad is intended to provide both heat and light, and provides no means for cooling the diodes or infant.
There is still a need, therefore, for a phototherapy device that provides high irradiance to a large surface area of the neonate, is inexpensive, consumes relatively low power, can be used outside of a hospital, minimizes discomfort to the neonate and caregivers, operates at the desired wavelength range, and is completely safe for the neonate.
Accordingly, it is a primary object of the present invention to provide a phototherapy garment that provides high irradiance to a maximum surface area of a neonate, thereby providing for rapid reduction in serum bilirubin levels.
It is an additional object of the invention to provide a phototherapy device in which light is generated directly adjacent to the neonate""s skin without overheating the neonate.
It is another object of the invention to provide a phototherapy garment that is lightweight and portable, allowing the neonate to be treated at home or while in transit.
It is a further object of the invention to provide a phototherapy garment that prevents light from reaching the neonate""s eyes, thereby eliminating the need for an eye shield and preventing nausea in nursery staff.
It is another object of the present invention to provide a phototherapy device that provides light that is completely safe to the neonate and causes few if any detrimental side effects.
It is an additional object of the invention to provide a phototherapy garment that is relatively inexpensive and consumes little power.
It is another object of the present invention to provide a phototherapy garment that fully covers the neonate, thereby preventing discomfort and hypothermia.
It is a further object of the invention to provide a phototherapy garment that does not inhibit maternal-infant contact and bonding.
It is an additional object of the invention to provide a phototherapy garment incorporating skin sensors that provide feedback to control activation of the light-emitting diodes.
Finally, it is an object of the invention to provide a phototherapy garment that communicates with a monitoring system using a two-way communications device, allowing remote control and recording of the garment""s operating parameters.
These objects and advantages are attained by a phototherapy garment for treating neonatal hyperbilirubinemia, Crigler-Najjar syndrome, and the like. The garment contains a flexible backing material, a liner sealed to the inside surface of the backing material, and a printed circuit sheet, preferably flexible, secured inside a pocket between the backing material and the liner. The printed circuit sheet contains a printed circuit and a plurality of surface-mounted light-emitting diodes (LEDs) facing the liner, preferably arranged in a densely packed array and generating light that is uniform across the surface of the garment. For example, there may be approximately 16 LEDs per square inch. The array has a longitudinal direction and a transverse direction, and the garment is preferably flexible in the longitudinal direction and the transverse direction. Preferably, the printed circuit sheet covers a majority of the inside surface of the backing material. The LEDs emit light of a wavelength suitable for treating hyperbilirubinemia in neonates, such as 420-500 nm, preferably between 440 and 470 nm. Portions of the backing material, liner, and flexible sheet may be removed to facilitate heat removal through the removed portions, and a heat sink material may also be provided.
The garment may also include a power supply, preferably portable, in electrical communication with the printed circuit for supplying power to the LEDs. The power supply may include means for supplying power intermittently and means for overdriving the LEDs. Preferably, the LEDs are supplied with enough power to generate an irradiance of greater than 30 xcexcW/cm2/nm, and most preferably greater than 100 xcexcW/cm2/nm. The garment may also contain a communications device, preferably wireless and two-way, for controlling and recording the parameters of LED operation. It may also contain sensors for measuring skin reflectance, as an index for the serum bilirubin concentrations, or properties such as skin temperature, oxygen saturation, glucose blood level, and perspiration.
Adjacent portions of the edge of the backing material may be joined together to define an interior space surrounded by the liner and in which a neonate is placed. Various garments, such as hats, sweaters, jackets, rompers, and sacs, may be formed. In these embodiments, the outer layer of the garment is a flexible shell with the desired shape, and a liner is sealed to the inside surface of the shell, with the printed circuit sheet positioned in between.
The present invention also provides a method of treating a neonate for hyperbilirubinemia including the steps of: providing a garment with a plurality of surface-mounted LEDs that emit light at a wavelength suitable for treating hyperbilirubinemia; covering a skin region of the neonate with the garment so that the LEDs face the skin region; and providing sufficient power to the LEDs to activate them. Preferably, the garment covers a majority of the circumference of the skin region that is being exposed to the light. Power is preferably provided to the LEDs intermittently, with a predetermined frequency and a predetermined duty cycle, which is preferably less than 50%, and most preferably approximately 10%. The method may also include measuring the bilirubin level in the skin, which is related to the pigment""s concentration in circulating blood of the neonate. The jaundice level of the skin is used to control activation, intensity, and duty cycle of the LEDs. The method may also include controlling LED activation remotely. The method can also be used to treat a patient with Crigler-Najjar syndrome.